The goal of the proposed research program is to gain basic knowledge concerning hypothalamic control of food-intake and body-weight regulation at both the behavioral and metabolic levels. In essence, the work is trying to elucidate the metabolic information channels that interact at the hypothalamic level to produce changes in energy regulatory behaviors of animals. We are presently mathematically analyzing the free feeding patterns of rats under a variety of metabolic conditions and after hypothalamic lesions. In other lines of research we are measuring hypothalamic oxygen consumption under a number of different metabolic conditions and correlating these with ongoing food intake. Similarly, we are measuring the distribution of nutrients in hypothalamic subareas after administration of radiolabelled nutrients. These studies indicate that the ventromedial hypothalamus may contain a mechanism which monitors long-term nutrient transactions which are expressed in ongoing feeding behavior. Studies employing intrahypothalamic injections of nutrients support this conclusion since glucose injections into the ventromedial hypothalamus can suppress feeding in the long-term but not immediately following injections. In addition to analyzing basic hypothalamic mechanisms for energy-balance maintenance, we are testing a variety of drugs, for instance (-)-hydroxycitrate, which might be useful therapeutic tools in controlling appetite. BIBLIOGRAPHIC REFERENCES: Panksepp, J., and Meekr, R. Suppression of food intake in diabetic rats by voluntary consumption and intrahypothalamic injection of glucose. Physiology and behavior, 1976, in press. Panksepp, J., Meeker, R., Reilly, P., and Vilberg, T. Reversible CNS lesions and disruption of self-stimulation by inhibition of axoplasmic flow. In A. Wauquier and E. T. Rolls (Eds.), Brain stimulation reward. Amsterdam: North Holland Publ., 1976, in press.